Polyphenolics (also known as phenolics) are metabolites found in plants, fruits, and vegetables. Phenolics have a number of functions including acting as free radical scavengers. Thus, phenolics disrupt many biological processes. The most notable type of phenolics are flavonoids which consist of proanthocyanidins, anthocyanidins, flavones, flavonols and their glycosides (Macheix, 1990). Anthocyanins are responsible for the red, purple, and blue colors of many fruits and vegetables. The term anthocyanin refers to a group of pigments found in plants, fruits, and vegetables that can be classified as both flavonoid and phenolic. Anthocyanins are not found in animals, microorganisms, or marine plants. It is thought that anthocyanins function by attracting insects to promote pollination but also to protect the plants from damage caused by ultraviolet (UV) radiation. Anthocyanins are glycosides of polyhydroxyl and polymethoxyl derivatives of 2-phenylbenzopyrylium or flavylium salts, and are soluble in water. The anthocyanins are electron deficient, and are therefore are strong scavengers for reactive oxygen species (ROS) such as free radicals. Although there are hundreds of different anthocyanins found in nature, six anthocyanin compounds predominate including: delphinidin, petunidin, cyanidin, pelargonidin, peonidin, and malvidin. The daily intake of anthocyanins in the United States is about 180-215 mg/day, and constitute the largest intake of phenolic compounds (Hertog, 1993).
Anthocyanins originally drew interest due to their role in color degradation in fruits, and their potential use as natural food colorants. More recently, anthocyanins have received attention because of their possible health benefits as natural antioxidant and anti-inflammatory compounds, and potentially as anti-cancer compounds. Antioxidant property, effects, or activity refers to compositions that inhibit, reduce, or reverse oxidation or the effects of oxidation, such as for example the oxidative process caused by free radicals. A free radical may be any chemical species that includes one or more unpaired electrons, and without limitations includes chemicals such as hydroxyl radical, superoxide radical, nitric oxide, and nitrogen dioxide. Examples of conditions involving free radical oxidative damage include, but are not limited to, aging, disease, stress, ultraviolet radiation, exercise, cancer, smoking, atherosclerosis, and chronic inflammation. Studies showed that antioxidant activity of cyanidins was greater than that of vitamin E and Trolox, and comparable to that of butylated hydroxytoluene (BHT) and butylated hydroxyanisole (BHA) (Wang et al., 1997; Rice-Evans et al., 1995; Liu et al., 2002; Proteggente et al., 2002; Wang et al., 1999).
Inflammation, or the biological state of being inflamed, is generally characterized by pain, redness, and swelling, and may result from physical causes such as injury, chemical causes such as exogenous substances including toxins, or biological causes such as infection by a virus, a bacteria, a parasite, or other disease-causing agent. As examples, various conditions associated with inflammation of the gastrointestinal tract are known, including but not limited to acute or chronic conditions or diseases such as inflammatory bowel disease, gastroesophageal reflux disease, diarrhea, radiation-induced enteritis, chemotherapy-induced enteritis, Crohn's disease, irritable bowel syndrome, diverticulitis, ulcers, colitis, viral infection, bacterial infection, and parasitic infection or infestation. In individuals afflicted with the above and similar conditions, affected cells such as dendritic cells, monocytes, macrophages, fibroblasts, endothelial cells, and T cells release causative agents, including cytokines such as interleukins (IL), tumor necrosis factor (TNF), interferons (IFN), and the like which trigger inflammation and/or an inflammatory response. Cytokines important in inflammation include, but are not limited to, IL-1, IL-6, IL-12, TNF-α, and IFN-α. Anti-inflammatory properties, effects, or activity refers to reducing inflammation and promoting healing of cells and tissues subject to inflammation and/or inflammatory processes.
Anti-cancer property, effect, or activity refers to a property of a substance, chemical, or material that can slow the proliferation of tumor cells (termed anti-proliferative effect), or kill tumor cells (termed cytotoxic effect). Recent studies have shown also that berries such as black raspberries possess cancer-preventing properties at both in-vitro and in-vivo levels (Kresty et al., 2001; Castro et al., 2002; Xue et al., 2001; Huang et al., 2002; Rodrigo et al, in press; U.S. patent application Ser. No. 10/951,413). In particular, anthocyanins have been shown to demonstrate a wealth of chemopreventive properties (Hecht et al., in press; Liu et al., 2002; Katsube et al., 2003; Hu et al., 2003).
However, anthocyanin compounds are inherently unstable both in vivo and in vitro, and tend to degrade over time, negating any health or medical benefits associated therewith (Rubinskiene et al., 2005; Nielsen et al., 2003; Morais et al., 2002). A need in the art therefore exists for methods for preparing compositions from anthocyanin-containing fruits such as berries which provide a stable anthocyanin content. Still further, there is a need for compositions including such stable anthocyanin compositions to provide health and medical benefits to individuals utilizing them. In particular, compositions formulated for oral administration and topical administration are described herein. However, it will be appreciated that other formulations are contemplated and can be derived by the skilled artisan from the teachings herein using methods known in the art, including injectable formulations. Accordingly, the present invention contemplates also injectable formulations including, but not limited to, solutions, suspensions, emulsion, microemulsions, micelles, liposomes, nanoparticles, microparticles, implants, depots, and polymer conjugates.